Open Label Extension in Adults With Binge Eating Disorder (BED)

A Phase 3, Multicenter, Open-label, 12 Month Extension Safety and Tolerability Study of SPD489 in the Treatment of Adults With Binge Eating Disorder

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01657019

Enrollment

604

Registered

2012-08-03

Start date

2012-08-21

Completion date

2014-10-21

Last updated

2021-06-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Binge Eating Disorder

Brief summary

To evaluate the safety and tolerability of SPD489 administered as a daily morning dose (50 or 70mg) in the treatment of moderate to severe binge eating disorder (BED) in adults

Interventions

DRUGLisdexamfetamine dimesylate

50 or 70 mg administered orally, once a day for 52 weeks

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Inclusion criteria

1. Completion of an antecedent SPD489 BED Double-blind Study 2. Subject meets the following Diagnostic and Statistical Manual of Mental Disorders Fourth Edition - Text Revision (DSM-IV-TR) criteria for a diagnosis of BED 3. Subject has a body mass index (BMI) of \> or =18 and \< or =45

Exclusion criteria

1. Subject has concurrent symptoms of bulimia nervosa or anorexia nervosa. 2. Subject is considered a suicide risk or risk to harm others

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) as a Measure of Safety	52 weeks	—
Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS)	53 weeks	Suicidality was assessed by using the C-SSRS, a semi-structured interview designed to capture the occurrence, severity, and frequency of suicide-related thoughts and behaviors. The interview and rating for the C-SSRS was completed by a clinician who had been successfully trained by the sponsor or designee. The interview was initiated with 5 (yes/no) questions, presented in ascending order of severity, about suicidal ideation. The most severe type of ideation was rated for frequency, duration, controllability, deterrents, and reason. If the answers to the first 2 ideation questions were yes, the clinician asked questions 3-5. Active suicidal ideation included any participant who answered yes to questions 2-5. If the answers to ideation questions 1 and 2 were no, then the clinician proceeded to 5 (yes/no) questions that addressed suicidal behavior, which was categorized as actual attempt, interrupted attempt, aborted attempt, preparatory acts or behaviors, and completed suicide.

Secondary

Measure	Time frame	Description
Percentage of Participants With a Response to The EuroQoL Group 5 Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Mobility	End of Treatment (ET; either Visit 16 [Week 52] or Early Termination)	The EQ-5D-5L is one of the most widely used generic index measures of health-related quality of life. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. The percentages of participants with various responses to the mobility questionnaire are reported. Percentages are based on all participants in the Full Analysis Set with a valid result at the given visit.
Percentage of Participants With a Response to The EuroQoL Group 5 Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care	End of Treatment (ET; either Visit 16 [Week 52] or Early Termination)	The EQ-5D-5L is one of the most widely used generic index measures of health-related quality of life. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. The percentages of participants with various responses to the self care questionnaire are reported. Percentages are based on all participants in the Full Analysis Set with a valid result at the given visit.
Percentage of Participants With an Improved Response on The Clinical Global Impressions of Improvement (CGI-I) Scale	Weeks 1, 4, 24, and 52, and end of treatment (either Visit 16 [Week 52] or Early Termination)	The CGI rating scales permitted the global evaluation of a participant's condition severity and improvement over time. The CGI-I was performed to rate the improvement of a participant's condition on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) and included a 'not assessed' option. The responses were dichotomized into 2 categories (improved or not improved). Improved included very much improved and much improved; not improved included minimally improved, no change, minimally worse, much worse, and very much worse. Not assessed and missing values were excluded from the percentage calculation.
Percentage of Participants With a Response to The EuroQoL Group 5 Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort	End of Treatment (ET; either Visit 16 [Week 52] or Early Termination)	The EQ-5D-5L is one of the most widely used generic index measures of health-related quality of life. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. The percentages of participants with various responses to the pain/discomfort questionnaire are reported. Percentages are based on all participants in the Full Analysis Set with a valid result at the given visit.
Percentage of Participants With a Response to The EuroQoL Group 5 Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety or Depression	End of Treatment (ET; either Visit 16 [Week 52] or Early Termination)	The EQ-5D-5L is one of the most widely used generic index measures of health-related quality of life. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. The percentages of participants with various responses to the anxiety/depression questionnaire are reported. Percentages are based on all participants in the Full Analysis Set with a valid result at the given visit.
Percentage of Participants With a Response to The EuroQoL Group 5 Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities	End of Treatment (ET; either Visit 16 [Week 52] or Early Termination)	The EQ-5D-5L is one of the most widely used generic index measures of health-related quality of life. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. The percentages of participants with various responses to the usual activities questionnaire are reported. Percentages are based on all participants in the Full Analysis Set with a valid result at the given visit.
Change From Baseline in The Global Score for The Eating Disorder Examination Questionnaire (EDE-Q)	Baseline, Weeks 4, 24, and 52, and end of treatment (either Visit 16 [Week 52] or Early Termination)	The EDE-Q is a 28-item questionnaire measuring eating pathology and is derived directly from the Eating Disorder Examination Interview. The EDE-Q focuses on the past 28 days to assess the main behavioral (eating and purging) and attitudinal features of eating disorders. The 28 items are rated by the participant on a 7-point scale (ranging from 0 to 6), with higher scores indicating increased pathology. The EDE-Q includes 4 subscales: Restraint, Eating Concern, Weight Concern, and Shape Concern. The global score is the average of all 28 items, with a range of 0 to 6. A negative value indicates a favorable result. The values presented are the mean change from baseline.

Countries

Germany, Spain, United States

Participant flow

Recruitment details

This was an open-label extension study to evaluate the long-term safety of SPD489 in adults aged 18-55 years with binge eating disorder (BED) who completed 1 of 3 antecedent studies, all of which tested SPD489 for BED (SPD489-208, SPD489-343, or SPD489-344).

Participants by arm

Arm	Count
All Participants Participants initially received lisdexamfetamine dimesylate, 30 mg administered orally, once daily during the dose optimization phase, regardless of their treatment assignment in the antecedent study. The dose was increased to an optimal dose of either 50 or 70 mg administered orally, once daily. Participants received treatment for a total of 52 weeks, then were followed for 1 week.	599
Total	599

Arm

Count

All Participants

Participants initially received lisdexamfetamine dimesylate, 30 mg administered orally, once daily during the dose optimization phase, regardless of their treatment assignment in the antecedent study. The dose was increased to an optimal dose of either 50 or 70 mg administered orally, once daily. Participants received treatment for a total of 52 weeks, then were followed for 1 week.

599

Total

599

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	55
Overall Study	Lack of Efficacy	3
Overall Study	Lost to Follow-up	48
Overall Study	Other	58
Overall Study	Protocol Violation	6
Overall Study	Withdrawal by Subject	65

Baseline characteristics

Characteristic	All Participants
Age, Continuous	39.0 years STANDARD_DEVIATION 9.98
Age, Customized < 40 years	301 Participants
Age, Customized >/= 40 years	298 Participants
Sex: Female, Male Female	521 Participants
Sex: Female, Male Male	78 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	447 / 599
serious Total, serious adverse events	17 / 599

Outcome results

Primary

Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS)

Suicidality was assessed by using the C-SSRS, a semi-structured interview designed to capture the occurrence, severity, and frequency of suicide-related thoughts and behaviors. The interview and rating for the C-SSRS was completed by a clinician who had been successfully trained by the sponsor or designee. The interview was initiated with 5 (yes/no) questions, presented in ascending order of severity, about suicidal ideation. The most severe type of ideation was rated for frequency, duration, controllability, deterrents, and reason. If the answers to the first 2 ideation questions were yes, the clinician asked questions 3-5. Active suicidal ideation included any participant who answered yes to questions 2-5. If the answers to ideation questions 1 and 2 were no, then the clinician proceeded to 5 (yes/no) questions that addressed suicidal behavior, which was categorized as actual attempt, interrupted attempt, aborted attempt, preparatory acts or behaviors, and completed suicide.

Time frame: 53 weeks

Population: The Safety Analysis Set, defined as all participants who took at least 1 dose of investigational product and who had at least 1 post-Visit 0 safety assessment in the study.

Arm	Measure	Group	Value (NUMBER)
All Participants	Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS)	Suicidal behavior	0 participants
All Participants	Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS)	Active suicidal ideation	2 participants
All Participants	Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS)	Non-suicidal self-injurious behavior	3 participants

Primary

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) as a Measure of Safety

Time frame: 52 weeks

Population: The Safety Analysis Set was defined as all participants who took at least 1 dose of investigational product and who had at least 1 post-Visit 0 safety assessment in the study.

Arm	Measure	Group	Value (NUMBER)
All Participants	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) as a Measure of Safety	Any TEAE	84.5 percentage of participants
All Participants	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) as a Measure of Safety	Serious TEAEs	2.8 percentage of participants

Secondary

Change From Baseline in The Global Score for The Eating Disorder Examination Questionnaire (EDE-Q)

The EDE-Q is a 28-item questionnaire measuring eating pathology and is derived directly from the Eating Disorder Examination Interview. The EDE-Q focuses on the past 28 days to assess the main behavioral (eating and purging) and attitudinal features of eating disorders. The 28 items are rated by the participant on a 7-point scale (ranging from 0 to 6), with higher scores indicating increased pathology. The EDE-Q includes 4 subscales: Restraint, Eating Concern, Weight Concern, and Shape Concern. The global score is the average of all 28 items, with a range of 0 to 6. A negative value indicates a favorable result. The values presented are the mean change from baseline.

Time frame: Baseline, Weeks 4, 24, and 52, and end of treatment (either Visit 16 [Week 52] or Early Termination)

Population: The Full Analysis Set, defined as all participants in the Safety Analysis Set who had at least 1 post-Visit 0 clinical experience outcome assessment in this study. The Safety Analysis Set was defined as all participants who took at least 1 dose of investigational product and who had at least 1 post-Visit 0 safety assessment in the study.

Arm	Measure	Group	Value (MEAN)	Dispersion
All Participants	Change From Baseline in The Global Score for The Eating Disorder Examination Questionnaire (EDE-Q)	Visit 4 (Week 4), n=483	-1.66 units on a scale	Standard Deviation 1.156
All Participants	Change From Baseline in The Global Score for The Eating Disorder Examination Questionnaire (EDE-Q)	Visit 9 (Week 24), n=391	-1.95 units on a scale	Standard Deviation 1.271
All Participants	Change From Baseline in The Global Score for The Eating Disorder Examination Questionnaire (EDE-Q)	Visit 16 (Week 52), n=314	-1.95 units on a scale	Standard Deviation 1.261
All Participants	Change From Baseline in The Global Score for The Eating Disorder Examination Questionnaire (EDE-Q)	End of Treatment, n=503	-1.90 units on a scale	Standard Deviation 1.284

Secondary

Percentage of Participants With an Improved Response on The Clinical Global Impressions of Improvement (CGI-I) Scale

The CGI rating scales permitted the global evaluation of a participant's condition severity and improvement over time. The CGI-I was performed to rate the improvement of a participant's condition on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) and included a 'not assessed' option. The responses were dichotomized into 2 categories (improved or not improved). Improved included very much improved and much improved; not improved included minimally improved, no change, minimally worse, much worse, and very much worse. Not assessed and missing values were excluded from the percentage calculation.

Time frame: Weeks 1, 4, 24, and 52, and end of treatment (either Visit 16 [Week 52] or Early Termination)

Arm	Measure	Group	Value (NUMBER)
All Participants	Percentage of Participants With an Improved Response on The Clinical Global Impressions of Improvement (CGI-I) Scale	Visit 1 (Week 1), n=589	53.7 percentage of participants
All Participants	Percentage of Participants With an Improved Response on The Clinical Global Impressions of Improvement (CGI-I) Scale	Visit 4 (Week 4), n=572	88.5 percentage of participants
All Participants	Percentage of Participants With an Improved Response on The Clinical Global Impressions of Improvement (CGI-I) Scale	Visit 9 (Week 24), n=466	92.7 percentage of participants
All Participants	Percentage of Participants With an Improved Response on The Clinical Global Impressions of Improvement (CGI-I) Scale	Visit 16 (Week 52), n=369	95.4 percentage of participants
All Participants	Percentage of Participants With an Improved Response on The Clinical Global Impressions of Improvement (CGI-I) Scale	End of Treatment, n=597	89.9 percentage of participants

Secondary

Percentage of Participants With a Response to The EuroQoL Group 5 Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety or Depression

The EQ-5D-5L is one of the most widely used generic index measures of health-related quality of life. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. The percentages of participants with various responses to the anxiety/depression questionnaire are reported. Percentages are based on all participants in the Full Analysis Set with a valid result at the given visit.